Glucuronidation is often involved in
drug metabolism of substances such as
drugs, pollutants,
bilirubin,
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s,
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
s,
mineralocorticoids,
glucocorticoids,
fatty acid derivatives,
retinoids, and
bile acids. These linkages involve
glycosidic bond
A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate.
A glycosidic bond is formed between the hemiacetal or hemiketal group ...
s.
Mechanism
Glucuronidation consists of transfer of the
glucuronic acid component of
uridine diphosphate glucuronic acid to a substrate by any of several types of
UDP-glucuronosyltransferase.
UDP-glucuronic acid (glucuronic acid linked via a
glycosidic bond
A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate.
A glycosidic bond is formed between the hemiacetal or hemiketal group ...
to
uridine diphosphate) is an intermediate in the process and is formed in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
. One example is the N-glucuronidation of an
aromatic amine
In organic chemistry, an aromatic amine is an organic compound consisting of an aromatic ring attached to an amine. It is a broad class of compounds that encompasses aniline
Aniline is an organic compound with the formula C6 H5 NH2. Consi ...
,
4-aminobiphenyl, by UGT1A4 or UGT1A9 from human, rat, or mouse liver.
:
The substances resulting from glucuronidation are known as
glucuronides (or glucuronosides) and are typically much more
water
Water (chemical formula ) is an Inorganic compound, inorganic, transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living ...
-
soluble
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solubi ...
than the non-glucuronic acid-containing substances from which they were originally synthesised. The human body uses glucuronidation to make a large variety of substances more water-soluble, and, in this way, allow for their subsequent elimination from the body through urine or feces (via bile from the liver).
Hormones are glucuronidated to allow for easier transport around the body. Pharmacologists have linked drugs to glucuronic acid to allow for more effective delivery of a broad range of potential therapeutics. Sometimes toxic substances are also less toxic after glucuronidation.
The conjugation of xenobiotic molecules with
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are ...
molecular species such as glucuronic acid is known as
phase II metabolism.
Sites
Glucuronidation occurs mainly in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
, although the enzyme responsible for its
catalysis,
UDP-glucuronyltransferase, has been found in all major body organs (e.g.,
intestine,
kidneys,
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
,
adrenal gland,
spleen, and
thymus).
General influencing factors
Various factors affect the rate of glucuronidation, which in turn will affect these molecules'
clearance from the body. Generally, an increased rate of glucuronidation results in a loss of potency for the target drugs or compounds.
Affected drugs
Many drugs which are substrates for glucuronidation as part of their metabolism are significantly affected by inhibitors or inducers of their specific glucuronisyltransferase types:
References
{{reflist
Hepatology
Organic reactions